Management of ANC <500 cells/µL
Patients with ANC <500 cells/µL require immediate risk stratification and initiation of prophylactic antimicrobials if high-risk, or empiric broad-spectrum antibiotics within 2 hours if febrile. 1, 2
Immediate Assessment
Temperature Monitoring
- Check temperature immediately – fever is defined as a single oral temperature ≥38.3°C (101°F) or ≥38.0°C (100.4°F) sustained for ≥1 hour 1, 2
- If febrile, this constitutes a medical emergency requiring empiric antibiotics within 2 hours 2
- If afebrile, proceed to risk stratification 1
Risk Stratification
High-risk patients include those with: 1, 2
- Expected prolonged neutropenia (>7 days)
- Profound neutropenia (ANC <100 cells/µL)
- Hematologic malignancy
- Recent intensive chemotherapy
- Allogeneic hematopoietic stem cell transplant
- Hemodynamic instability
- Mucositis or other comorbidities
Low-risk patients include those with: 1
- Expected brief neutropenia (<7 days)
- MASCC score ≥21
- Solid tumors
- No significant comorbidities
- Hemodynamically stable
Management Algorithm
For FEBRILE Patients (ANC <500 cells/µL + Fever)
High-Risk Febrile Neutropenia
Initiate IV monotherapy with antipseudomonal β-lactam within 2 hours: 1, 2
- Cefepime (preferred first-line agent) 2
- Alternatives: ceftazidime, meropenem, imipenem, or piperacillin-tazobactam 1, 2
- Suspected catheter-related infection
- Hemodynamic instability
- Known MRSA colonization
- Skin/soft tissue infection
- Hospital with high MRSA endemicity
Before initiating antibiotics, obtain: 2
- Blood cultures (two sets from different sites)
- Urine culture
- Chest X-ray
- Cultures from any suspected infection site
Low-Risk Febrile Neutropenia
Outpatient oral therapy is acceptable if ALL criteria met: 1
- MASCC score ≥21
- No hemodynamic instability
- No organ dysfunction
- Adequate oral intake
- Reliable follow-up available
Oral regimen: 1
- Ciprofloxacin 500 mg twice daily PLUS amoxicillin-clavulanate (preferred) 1
- Alternative: levofloxacin monotherapy or ciprofloxacin plus clindamycin 1
- Do NOT use fluoroquinolone if patient already on fluoroquinolone prophylaxis 1
For AFEBRILE Patients (ANC <500 cells/µL, No Fever)
High-Risk Afebrile Patients (Expected Neutropenia >7 Days)
Initiate fluoroquinolone prophylaxis: 1, 2
- Levofloxacin 500 mg orally daily (preferred, especially with mucositis risk) 1, 2
- Alternative: ciprofloxacin 500 mg orally daily 1
- Continue until ANC >500 cells/µL 1
Additional prophylaxis for high-risk patients: 1, 2
- Antifungal: Fluconazole 400 mg orally daily (start at anticipated nadir, stop when ANC >1000 cells/µL) 2
- PCP prophylaxis: Trimethoprim-sulfamethoxazole three times weekly (continue 6 months or until CD4 >200 cells/mm³) 1, 2
- Antiviral: Acyclovir 400 mg or valacyclovir 500 mg orally twice daily (continue 6 months or until lymphocyte recovery) 2
Low-Risk Afebrile Patients (Expected Neutropenia <7 Days)
- Antibacterial prophylaxis NOT routinely recommended 1
- Monitor temperature every 4-6 hours 2
- Educate patient to seek immediate care if fever develops 1
Granulocyte Colony-Stimulating Factor (G-CSF)
Indications for G-CSF (Filgrastim 5 mcg/kg/day subcutaneously): 2, 3, 4
- High-risk patients with expected prolonged neutropenia (>7 days)
- ANC <100 cells/µL
- Post-chemotherapy when severe neutropenia anticipated
- Continue until ANC ≥500 cells/µL for two consecutive days 2, 3
CONTRAINDICATIONS to G-CSF: 2, 3
G-CSF is NOT routinely recommended for: 1
- Standard febrile neutropenia management
- Low-risk patients
Monitoring Requirements
Daily while ANC <500 cells/µL: 2
- Complete blood count with differential
- Temperature checks every 4-6 hours
- Clinical assessment for infection signs
Transfusion thresholds: 2
- Platelets: transfuse if <30,000/mm³
- Packed red blood cells: transfuse if hemoglobin <7.0 g/dL
- Use only irradiated blood products 2
Modification of Therapy
If Patient Becomes Afebrile by Day 3-5
If no pathogen identified and ANC recovering (>500 cells/µL): 1, 2
- Continue antibiotics until afebrile for ≥48 hours AND ANC >500 cells/µL 1, 2
- Discontinue when blood cultures negative for 48 hours 1, 2
If no pathogen identified and ANC remains <500 cells/µL: 1, 2
- Low-risk patients: Continue IV antibiotics for 5-7 days total 1, 2
- High-risk patients: Continue IV antibiotics until ANC recovery 1, 2
If Fever Persists Beyond Day 3
Reassess for: 1
- Resistant organisms (MRSA, VRE, ESBL, KPC)
- Fungal infection
- Non-infectious causes
- Inadequate source control
If fever persists 4-7 days: 1, 2
- Add empiric antifungal therapy (especially if expected neutropenia >7 days) 1, 2
- Obtain CT chest and sinuses 1
- Consider galactomannan or beta-D-glucan testing 1
If ANC >500 cells/µL: 1
- Stop antibiotics 4-5 days after ANC >500 cells/µL 1
If ANC remains <500 cells/µL: 1
Duration of Antibiotic Therapy
For documented infections: 1
- Continue appropriate antibiotics for at least the duration of neutropenia (until ANC >500 cells/µL) or longer if clinically necessary 1
For unexplained fever: 1
- Continue initial regimen until clear signs of marrow recovery (ANC >500 cells/µL) 1
- Alternatively, if treatment course completed and all signs/symptoms resolved, may resume oral fluoroquinolone prophylaxis until marrow recovery 1
Critical Pitfalls to Avoid
- Do NOT delay empiric antibiotics while awaiting culture results in febrile patients – the 2-hour window is mandatory 2
- Do NOT withhold antibacterial prophylaxis in high-risk patients (>7 days expected neutropenia) even if currently afebrile 1, 2
- Do NOT stop antibiotics prematurely in persistently neutropenic patients – therapy must continue until ANC recovery 1, 2
- Do NOT use G-CSF during active chest radiation due to increased mortality risk 2, 3
- Do NOT use fluoroquinolone empiric therapy in patients already on fluoroquinolone prophylaxis 1
- Do NOT forget irradiated blood products for severely immunocompromised patients 2
- Do NOT add vancomycin empirically unless specific risk factors present (catheter infection, MRSA colonization, hemodynamic instability) 1, 2